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Graft-Versus-Host Disease

Absence of IL-23p19 in donor allogeneic cells reduces mortality from acute GVHD

Bone Marrow Transplantation volume 45, pages 712–722 (2010)Cite this article

Abstract

The p19 dimer of interleukin 23 (IL-23) has been reported to have a major role in the pathogenesis of many experimental and clinical autoimmune diseases and may also have a prominent role in transplantation. We reasoned that deficiency of p19 in the allogeneic donor transplant might reduce the inflammation caused by acute GVHD (aGVHD). The major histocompatibility complex-2 (H2d) BALB/c mice were subjected to 8.5 Gy TBI, followed by transplantation with 10 × 106 BM and 2.5 × 106 spleen cells from H2d BALB/c, H2b C57Bl/6 (B6) or H2b p19−/− donors. In all, 75% of the p19−/− transplanted mice survived, compared with only 12.5% of the B6 transplanted mice. This superior survival is correlated with significantly less severe aGVHD, absence of p19 after transplantation, less upregulation of mRNA and lower serum levels of IL-17 as compared with the B6 transplants. TBI alone significantly upregulated transforming growth factor-β (TGF-β), IL-6 and p19 mRNA levels in host BALB/c mice, possibly providing the milieu to induce IL-17 in p19−/− donor cells. IL-22, another cytokine, the induction of which in T-helper 17 (Th17) cells is supported by p19, was upregulated in BALB/c hosts but not in transplanted B6 or p19 donor cells, and may not have had a major role in modifying aGVHD.

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Acknowledgements

This study was supported by Merit Review and Type II Merit Review Grants from the Veterans and also by the Administration and a University of Kentucky Research Graduate Studies award.

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Authors and Affiliations

  1. Veterans Affairs Medical Center, University of Kentucky, Lexington, KY, USA

    J S Thompson & S A Brown

  2. Department of Internal Medicine, University of Kentucky, Lexington, KY, USA

    J S Thompson, Y Chu, J F Glass & S A Brown

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  1. J S Thompson
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Correspondence to J S Thompson.

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Thompson, J., Chu, Y., Glass, J. et al. Absence of IL-23p19 in donor allogeneic cells reduces mortality from acute GVHD. Bone Marrow Transplant 45, 712–722 (2010). https://doi.org/10.1038/bmt.2009.215

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